Normoxic re-oxygenation ameliorates end-organ injury after cardiopulmonary bypass.

BACKGROUND In a rabbit model of cardiopulmonary bypass (CPB) and cardioplegic arrest, we previously showed that hyperoxic myocardial reperfusion was associated with increased left ventricular (LV) systolic dysfunction and myocardial injury compared with normoxic reperfusion. The aim of this study was to evaluate in our experimental model the impact of post-CPB reperfusion conditions on other organs potentially vulnerable to ischemic injury such as the brain and kidney. METHODS After 60 min of CPB, aortic cross-clamp, and cold cardioplegic arrest, rabbits were reperfused under hyperoxic or normoxic conditions for 120 min. Left ventricular systolic contractility (LV + dP/dt) and diastolic relaxation (LV -dP/dt) were continuously recorded, and end-organ injury was assessed by measuring circulating biomarkers specific for kidney (cystatin C and creatinine) and brain injury [S100B and neuron specific enolase (NSE)]. At completion of the protocol, kidney and brain tissues were harvested for measuring oxidant stress (OS), inflammation and apoptosis. RESULTS Following aortic cross-clamp removal, rabbits exposed to normoxic reperfusion demonstrated preserved LV systolic and diastolic function compared with hyperoxic reperfusion (LV + dP/dt: 70 ± 14% of pre-CPB vs. 36 ± 21%, p = 0.018; LV -dP/dt: 72 ± 36% of pre-CPB vs. 33 ± 20%, p = 0.023). Similarly, CPB increased plasma creatinine, S100B and NSE that were significantly attenuated by normoxic reperfusion compared with hyperoxic reperfusion (creatinine: 4.0 ± 0.5 vs. 7.1 ± 0.8 mg/dL, p = 0.004; S100B: 4.0 ± 0.8 vs. 6.7 ± 1.0 ng/mL, p = 0.047; NSE: 57.7 ± 6.8 vs. 101.3 ± 16.1 pg/mL, p = 0.040). Furthermore, both kidney and brain tissues showed increased mRNA expression and activation of pathways for OS, inflammation, and apoptosis, that were reduced under normoxic compared with hyperoxic conditions. CONCLUSIONS Normoxic reperfusion ameliorates cardiac, renal and neural injury compared with hyperoxic reperfusion in an in vivo animal model of CPB and cardioplegic arrest. This protective effect of normoxic reperfusion may be due to a reduction in signaling pathways for OS, inflammation, and apoptosis.